A major therapeutic goal in the treatment of diabetes is the physiological control of blood glucose levels. Many different commercial products and formulations are available for this purpose. For the rapid rise in glucose challenge that occurs at mealtimes, the fast-acting insulin products, such as Humulin Regular or the so-called monomeric insulin analogs are most appropriate.
Another important source of glucose load in patients is the low-level, basal glucose output from the liver. This output results primarily from postprandial metabolic processes such as gluconeogenesis and glycogenolysis. In diabetic subjects, this basal glucose output can increase substantially at night and result in extended periods of hyperglycemia, especially during the early morning hours in an incident referred to as the dawn phenomenon. These periods of hyperglycemia have been shown to be an important contributor to high levels of glycated proteins, often measured clinically as glycosylated hemoglobin. Buildup of these derivatized protein products is implicated in the long-term complications associated with diabetes such as neuropathy, nephropathy and retinopathy.
The ideal insulin formulation to deal with this basal glucose output would be one that resulted in a slow, steady infusion of insulin into the bloodstream that matched the low level of glucose output from the liver. In terms of this ideal basal time action, the best parenteral product that fits this description is commercially available beef Ultralente insulin. Injected just once per day, it gives a low, steady release of insulin into the bloodstream without any noticeable insulin peak.
A major problem with beef Ultralente, however, stems from the fact that beef insulin is different in amino acid sequence from human insulin. The human body can recognize bovine insulin as a foreign protein. Chronic injection of this immunogenic substance in diabetic patients can result in the formation of antibodies to the insulin. This can lead to alterations in insulin time action and potency and other problems arising from the patient's activated immune system. For these reasons beef Ultralente remains a non-ideal parenteral insulin formulation.